176 research outputs found
Discrete cilia modelling with singularity distributions
We discuss in detail techniques for modelling flows due to finite and infinite arrays of beating cilia. An efficient technique, based on concepts from previous ‘singularity models’ is described, that is accurate in both near and far-fields. Cilia are modelled as curved slender ellipsoidal bodies by distributing Stokeslet and potential source dipole singularities along their centrelines, leading to an integral equation that can be solved using a simple and efficient discretisation. The computed velocity on the cilium surface is found to compare favourably with the boundary condition. We then present results for two topics of current interest in biology. 1) We present the first theoretical results showing the mechanism by which rotating embryonic nodal cilia produce a leftward flow by a ‘posterior tilt,’ and track particle motion in an array of three simulated nodal cilia. We find that, contrary to recent suggestions, there is no continuous layer of negative fluid transport close to the ciliated boundary. The mean leftward particle transport is found to be just over 1 μm/s, within experimentally measured ranges. We also discuss the accuracy of models that represent the action of cilia by steady rotlet arrays, in particular, confirming the importance of image systems in the boundary in establishing the far-field fluid transport. Future modelling may lead to understanding of the mechanisms by which morphogen gradients or mechanosensing cilia convert a directional flow to asymmetric gene expression. 2) We develop a more complex and detailed model of flow patterns in the periciliary layer of the airway surface liquid. Our results confirm that shear flow of the mucous layer drives a significant volume of periciliary liquid in the direction of mucus transport even during the recovery stroke of the cilia. Finally, we discuss the advantages and disadvantages of the singularity technique and outline future theoretical and experimental developments required to apply this technique to various other biological problems, particularly in the reproductive system
Aging display's effect on interpretation of digital pathology slides
It is our conjecture that the variability of colors in a pathology image
effects the interpretation of pathology cases, whether it is diagnostic
accuracy, diagnostic confidence, or workflow efficiency. In this paper, digital
pathology images are analyzed to quantify the perceived difference in color
that occurs due to display aging, in particular a change in the maximum
luminance, white point, and color gamut. The digital pathology images studied
include diagnostically important features, such as the conspicuity of nuclei.
Three different display aging models are applied to images: aging of luminance
& chrominance, aging of chrominance only, and a stabilized luminance &
chrominance (i.e., no aging). These display models and images are then used to
compare conspicuity of nuclei using CIE deltaE2000, a perceptual color
difference metric. The effect of display aging using these display models and
images is further analyzed through a human reader study designed to quantify
the effects from a clinical perspective. Results from our reader study indicate
significant impact of aged displays on workflow as well as diagnosis as follow.
As compared to the originals (no-aging), slides with the effect of aging
simulated were significantly more difficult to read (p-value of 0.0005) and
took longer to score (p-value of 0.02). Moreover, luminance+chrominance aging
significantly reduced inter-session percent agreement of diagnostic scores
(p-value of 0.0418)
AIDS-Related EBV-Associated Smooth Muscle Tumors: A Review of 64 Published Cases
The number of reported cases of smooth muscle tumor (SMT) arising in patients with AIDS has been increasing since the mid-1990s. The aim of this study is to characterize the epidemiology, clinical manifestations, pathologic features, prognosis and, management of Epstein-Barr virus-related SMT (EBV-SMT) in patients with AIDS. An English language literature search identified 53 articles including 64 reported cases of EBV-SMT. The majority of these reports involved patients who were young, severely immunosuppressed, and had multifocal tumors. The central nervous system was the most common site to be involved. Histologically, tumors had smooth muscle features and were immunoreactive for muscle markers and all but two tumors demonstrated the presence of EBV by either immunohistochemistry, in situ hybridization, and/or PCR. While mitoses and/or necrosis were used to separate leiomyoma from leiomyosarcoma, these features did not correlate with clinical outcome. Treatment included primarily resection, and less often radiotherapy, chemotherapy and highly active antiretroviral therapy (HAART). Overall, EBV-SMTs appear to have variable aggressiveness and clinical outcome and may exhibit a more favorable prognosis compared to conventional leiomyosarcoma. Tumor-related death from EBV-SMT occurred in only 4 of 51 patients
Infinitary and Cyclic Proof Systems for Transitive Closure Logic
Transitive closure logic is a known extension of first-order logic obtained by introducing a transitive closure operator. While other extensions of first-order logic with inductive definitions are a priori parametrized by a set of inductive definitions, the addition of the transitive closure operator uniformly captures all finitary inductive definitions. In this paper we present an infinitary proof system for transitive closure logic which is an infinite descent-style counterpart to the existing (explicit induction) proof system for the logic. We show that, as for similar systems for first-order logic with inductive definitions, our infinitary system is complete for the standard semantics and subsumes the explicit system. Moreover, the uniformity of the transitive closure operator allows semantically meaningful complete restrictions to be defined using simple syntactic criteria. Consequently, the restriction to regular infinitary (i.e. cyclic) proofs provides the basis for an effective system for automating inductive reasoning
Hydrodynamic interaction in quasi-two-dimensional suspensions
Confinement between two parallel surfaces is found, theoretically and
experimentally, to drastically affect the hydrodynamic interaction between
colloid particles, changing the sign of the coupling, its decay with distance
and its concentration dependence. In particular, we show that three-body
effects do not modify the coupling at large distances as would be expected from
hydrodynamic screening.Comment: 8 pages, 2 figure
Active and driven hydrodynamic crystals
Motivated by the experimental ability to produce monodisperse particles in
microfluidic devices, we study theoretically the hydrodynamic stability of
driven and active crystals. We first recall the theoretical tools allowing to
quantify the dynamics of elongated particles in a confined fluid. In this
regime hydrodynamic interactions between particles arise from a superposition
of potential dipolar singularities. We exploit this feature to derive the
equations of motion for the particle positions and orientations. After showing
that all five planar Bravais lattices are stationary solutions of the equations
of motion, we consider separately the case where the particles are passively
driven by an external force, and the situation where they are self-propelling.
We first demonstrate that phonon modes propagate in driven crystals, which are
always marginally stable. The spatial structure of the eigenmodes depend solely
on the symmetries of the lattices, and on the orientation of the driving force.
For active crystals, the stability of the particle positions and orientations
depends not only on the symmetry of the crystals but also on the perturbation
wavelengths and on the crystal density. Unlike unconfined fluids, the stability
of active crystals is independent of the nature of the propulsion mechanism at
the single particle level. The square and rectangular lattices are found to be
linearly unstable at short wavelengths provided the volume fraction of the
crystals is high enough. Differently, hexagonal, oblique, and face-centered
crystals are always unstable. Our work provides a theoretical basis for future
experimental work on flowing microfluidic crystals.Comment: 10 pages, 10 figure
Dynamic Proteomics of Individual Cancer Cells in Response to a Drug
Why do seemingly identical cells respond differently to a drug? To address this, we studied the dynamics and variability of the protein response of human cancer cells to a chemotherapy drug, camptothecin. We present a dynamic-proteomics approach that measures the levels and locations of nearly 1000 different endogenously tagged proteins in individual living cells at high temporal resolution. All cells show rapid translocation of proteins specific to the drug mechanism, including the drug target (topoisomerase-1), and slower, wide-ranging temporal waves of protein degradation and accumulation. However, the cells differ in the behavior of a subset of proteins. We identify proteins whose dynamics differ widely between cells, in a way that corresponds to the outcomes—cell death or survival. This opens the way to understanding molecular responses to drugs in individual cells
Hydrodynamic Coupling of Two Brownian Spheres to a Planar Surface
We describe direct imaging measurements of the collective and relative
diffusion of two colloidal spheres near a flat plate. The bounding surface
modifies the spheres' dynamics, even at separations of tens of radii. This
behavior is captured by a stokeslet analysis of fluid flow driven by the
spheres' and wall's no-slip boundary conditions. In particular, this analysis
reveals surprising asymmetry in the normal modes for pair diffusion near a flat
surface.Comment: 4 pages, 4 figure
Screening by symmetry of long-range hydrodynamic interactions of polymers confined in sheets
Hydrodynamic forces may significantly affect the motion of polymers. In
sheet-like cavities, such as the cell's cytoplasm and microfluidic channels,
the hydrodynamic forces are long-range. It is therefore expected that that
hydrodynamic interactions will dominate the motion of polymers in sheets and
will be manifested by Zimm-like scaling. Quite the opposite, we note here that
although the hydrodynamic forces are long-range their overall effect on the
motion of polymers vanishes due to the symmetry of the two-dimensional flow. As
a result, the predicted scaling of experimental observables such as the
diffusion coefficient or the rotational diffusion time is Rouse-like, in accord
with recent experiments. The effective screening validates the use of the
non-interacting blobs picture for polymers confined in a sheet.Comment: http://www.weizmann.ac.il/complex/tlusty/papers/Macromolecules2006.pdf
http://pubs.acs.org/doi/abs/10.1021/ma060251
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